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Identifying Novel Fibrotic Mechanisms Underlying Treatment-Resistant Lower Urinary Tract Dysfunction
Full text linkABSTRACT
IDENTIFYING NOVEL FIBROTIC MECHANISMS UNDERLYING TREATMENT-RESISTANT LOWER URINARY TRACT DYSFUNCTION
August 2025
Quentin D’Arcy, B.S., University of Massachusetts Amherst
Ph.D., University of Massachusetts Boston
Directed by Dr. Jill Macoska
Lower urinary tract dysfunction (LUTD) is a common, age-related disease that affects millions of men over the age of 50. Current treatment for this and other related prostate diseases concentrate on decreasing benign prostate growth and relaxing smooth muscle contractions to alleviate urinary voiding symptoms. However, up to 45% of patients with LUTD are treatment-resistant and require surgical intervention to resolve prostate issues. By focusing on the contribution of inflammation-derived prostate fibrosis my project seeks to utilize a multi-part approach to close the gap between treatment receptive and treatment resistant LUTD. The first approach concerns the IL-4/IL-13 signaling pathway, a relatively unexplored fibrotic pathway which may be the key to dealing with inflammation-derived prostate fibrosis. The second approach looks at prostate supplements, which are notoriously understudied despite being taken by millions of men suffering from LUTD and BPH. The third approach explores the contribution of regulatory RNAs to pro-fibrotic mechanisms in prostate fibroblast. A better understanding of these factors could lead to the development of medical therapies that are readily tolerated by older patients and prevent the need for potentially risky surgical intervention for the aging patient pool experiencing LUTD.
The aims of my project seek to first identify the contribution of the IL-4/IL-13 signaling axis to extracellular matrix (ECM) upregulation in prostate fibroblasts and demonstrate its dependence on JAK/STAT signaling. Next, I will explore the response of human prostate fibroblasts to β-sitosterol, a plant sterol isolated from palmetto sawgrass which is the active ingredient in most commercially available prostate supplements. Finally, I will investigate the potential role of a newly explored class of RNA splicing isoforms, circular RNA (circRNA), in the regulation of fibrotic processes in response to IL-4/IL-13.
With such a large gap in treatment options for patients suffering from LUTD, there is a significant clinical need for better therapies to be developed. Since the patient population suffering from this disease is older, the surgical interventions that are currently used to treat LUTD have a much higher risk of collateral injury. By identifying the molecular mechanisms that underly the fibrotic condition of aging and inflammation in the prostate, my project could benefit patients by saving them both the pain and financial hardship associated with BPH/LUTD
Navigating the Unknown: Exploring the Lived Experiences of Middle-Aged Women from Post-Socialist Mongolia
No full textThis dissertation research examines the experiences of middle-aged Mongolian women during the transition from a planned socialist regime to a capitalist system. This period, marked by rapid shifts toward democracy and a market-based economy, resulted in profound systemic changes that transformed their lives. Despite these significant changes, limited research has focused on how this transition specifically impacted women, particularly in the aftermath of socialism. Using feminist phenomenology as a methodological framework, this qualitative study involved 48 middle-aged women through a timeline-assisted in-depth interview method. The findings reveal a complex life journey, emphasizing the resilience and resourcefulness of these women as they navigated both challenges and opportunities in a post-socialist context. The study shows that experiences of transition varied widely among participants. Some women achieved upward mobility through their resilience, while others faced insecure and unpredictable life paths. Many reported added socioeconomic vulnerabilities due to persistent unemployment, strained family relationships, and inadequate social support, which hindered their ability to build essential capabilities. This research emphasizes the importance of improving employment practices, ensuring equitable and affordable access to reskilling opportunities, and building strong economic and social support systems. These actions are vital for facilitating effective coping strategies and promoting long-term socioeconomic stability for women. By amplifying the voices of Mongolian women, this study advances the fields of women’s and gender studies, as well as studies of post-socialist countries. Lastly, this study calls for inclusive policies and practices that improve the lives of middle-aged women in Mongolia
Disruptive (Re)memberings: Anti-Blackness & The Mental Health of Black Millennial Womxn
Full text linkThis study examines the impact of anti-Blackness on the mental health of Black Millennial Womxn (BMW) pursuing post-secondary education. It explores the historical and contemporary factors that contribute to the neglect of Black Womxn in education research and the systemic issues that affect our access to mental health and educational resources. The research utilizes an Endarkened Feminist epistemology and narrative inquiry to center the narratives and lived experiences of BMW, challenging the prevailing narratives that erase our humxnity and intersectional identities. Data was collected through Black Participatory Research (BPR), individual interviews, and visual arts-based methods that center the lived experiences of Black Womxn. Key themes in the findings illuminate that though mental health is salient, socioeconomic inequities impede access to care which further increases the need for therapeutic interventions. Born from this research is Personal Welfare Reclamation (PWR), a praxis for people who inhabit Black bodies to reclaim their humxnity and well-being within anti-Black systems. This praxis is designed to disrupt the historical and ongoing erasure of Black people and consists of rituals that center humxnity through a critical, Black feminist, somatic lens
Accompanying Afghans: A Human Rights-Based Approach To Immigrant Mental Health
No full textIn light of the United States of America’s withdrawal from Afghanistan in August of 2021, the most recent wave of Afghans arriving across the U.S. has led to a call for increased attention towards access to mental health treatment following the displaced devastation. However, there has been a paucity of research on Afghan immigrants in the field of psychology since the arrival of the first large wave of Afghan refugees in the 1970’s and 80s, as well as a lack of Afghan voices in psychological research, training, and practice.
This qualitative study investigated the migratory experiences and mental health perspectives of first-generation Afghans who immigrated to the U.S. after the September 11 attacks and the invasion of Afghanistan, and prior to the U.S. evacuation of Afghanistan in August 2021, through a human rights-based lens rooted in psychologies of liberation and diaspora studies. The study employed semi-structured individual interviews with 15 Afghans living across the U.S.
The findings demonstrated that 4 main themes and 2 subthemes of “I felt I am inside a coffin:” Escaping and entering precarity, “American culture affected our Afghan culture:” Assimilation and the promise of neoliberal capitalism, “It makes you feel alive again:” Healing through community and the limits of psychotherapy, “Show them how to get on the bus:” The need for structural responsivity and epistemic curiosity, “They just give you pills…and it’s causing you to get worse:” How medicalization misses the mark, and “It doesn\u27t matter what language you speak, where are you from…we have to have one goal:” Community conflict and the importance of unity.
This study expands the literature on Afghan immigrants living in the U.S., providing the field of psychology with knowledge to better support this community through interventions that address systemic challenges that hinder the possibilities for well-being
On Being The Only: Using Black Feminist Thought and Hermeneutic Phenomenology to Deeply Understand Onliness as Experienced by Black Women in STEM
Full text linkWhen a Black woman persists in a STEM undergraduate academic space as the only Black woman in that space, how is she shaped as a human being? How does she fare? How does the experience influence her decision making as she contemplates graduate school applications? Does the experience guide her decision to stay or leave STEM? In this study, the author used Black Feminist Thought to provide cultural and critical oversight of her engagement with Hermeneutic Phenomenology. Hermeneutic Phenomenology requires this oversight because the methodology’s theoretical foundations are grounded in Heidegger’s Nazism and should be critiqued if and when appropriate to do so. The author engaged with eight Black women who self-identified as the only Black women in STEM undergraduate academic spaces—The Only. The author used qualitative research methodology to make meaning of the stories of each Only and to better understand the experience of being The Only. The stories were documented by first using a journaling exercise, followed by an individual interview with the researcher, and, lastly, participation in a Sista Circle. The study participants were from an array of colleges and universities across the United States. The study findings showed that the well-being of Black women is challenged when a Black woman is The Only. Participants often described feeling the need to “armor up” or to adapt to survive STEM environments. They also described feeling disappointed because they did not expect to be The Only, that they were not in community, and isolated, and they endured great pressure as The Only. Although these experiences influenced them as students and people, the Black women who were The Only in this study persisted to the graduate level in STEM
Analyzing the Role of a Novel Transmembrane Protein in Rhodopsin-Deficient Drosophila Photoreceptors
No full textVitamin A (vitA) is an essential nutrient and a precursor of the retinal chromophore, which is necessary for photoreceptor development and function. Chronic vitA deficiency causes photoreceptor death and is the leading cause of preventable childhood blindness. Like humans, Drosophila melanogaster requires vitA for Rhodopsin synthesis and vision but not for essential developmental processes or survival. Since chronic vitA deprivation in Drosophila does not lead to photoreceptor death, I hypothesized that an unknown molecular mechanism preserves photoreceptor structure and visual function.
In collaboration with the Shevchenko lab (MPI Dresden, Germany), I identified the novel transmembrane protein Mps, which responds to vitA deficiency and preserves the structure of Rhodopsin-deficient photoreceptor neurons. First, to understand how Mps is regulated, I analyzed Drosophila mutants with defective Rhodopsin 1 (Rh1) synthesis, ER stress, and malformed light-sensing compartments (rhabdomeres). While it has been challenging to identify a single causative factor, Mps expression strongly correlates with Rh1 processing defects and degradation. Second, I analyzed the function of a potential interactor of Mps, the scaffolding protein InaD. My data suggest that Mps anchors InaD to the rhabdomere membrane before the onset of Rh1 expression and that this Mps-InaD interaction is maintained in Rh1-deficient membranes to stabilize the rhabdomeres.
Taken together, these insights reveal how the interaction of a transmembrane protein and a scaffolding protein promote the survival of damaged photoreceptor neurons and could inspire novel therapeutic approaches to treat eye diseases
Give Them Their Roses: Honoring Student Affairs Professionals of Color Combatting Secondary Racial Battle Fatigue at a Historically White Institution
Full text linkThis dissertation explores the phenomenon of Secondary Racial Battle Fatigue (SRBF) and its impact on student affairs professionals of color in higher education. Grounded in critical qualitative inquiry and the lived experiences of participants, this study examines how emotional, behavioral, and physiological effects of SRBF manifest both through professionals’ direct racialized experiences and their roles supporting students enduring racial trauma. Framed by Racial Battle Fatigue (Smith, 2010) and Secondary Traumatic Stress (Figley, 1995), the research addresses three guiding questions: (a) How does SRBF manifest in professionals of color? (b) In what ways does it emerge when supporting racially traumatized students? and (c) How does SRBF shape professional practices in student affairs? Findings reveal that professionals of color are doubly impacted: first, through direct exposure to racial hostility and microaggressions within institutional environments, and second, through vicarious trauma while assisting students navigating bias incidents and racialized campus climates. Participants reported cumulative stress responses, including emotional exhaustion, hypervigilance, and disruptions to their physical and psychological well-being. The study highlights the urgent need for institutional accountability and the development of structured support systems to mitigate SRBF and its long-term effects. Implications include recommendations for policy reforms, leadership training, and wellness initiatives aimed at sustaining professionals of color in student affairs. By illuminating the nuanced experiences of these professionals, this research contributes to a deeper understanding of racialized labor in higher education and advocates for systemic change to foster equity and well-being
Parameter Estimation for Classical Dynamical Systems
No full textClassical measurement is a process that we carry out on nature, where the outcome exists with a numerical value, and the process of the measurement is to determine it with the best uncertainty. The improvement in precision of estimating a parameter is directly related to the amount of information available about the parameter. Since the the lower bound in Cramér-Rao inequality is the method providing the optimal precision, higher information leads to an improved Cramér- Rao lower bound, and thus implies a more precise estimate of the parameter. Understanding sources of information is the key to improving the precision of classical measurements, especially for some deterministic dynamical systems that have a form of measurable uncertainty. In this dissertation, we introduce a Fisher information as a method to measure the amount of information which we can extract from a system, and determined by the local curvature and the phase speed at each point along the phase space trajectory. Once the general structure of classical trajectories is more fully understood, we establish a relationship between the rate of contraction for an ensemble of dissipative trajectories and the logarithmic derivative that evolves a classical density matrix in a dynamical system. We also show that not only quantum measurements are able to give more precise estimates than classical statistics, but classical mechanical measurements can also, in principle, give more precise estimates than purely statistical measurements. We derive a statistical-mechanical Fisher information that upper bounds the purely statistical Fisher information and leads to an optimal lower bound on the uncertainty of the state of classical dynamical systems. Then, we define ratios that measure the classical mechanical advantage in parameter estimation within classical systems enhancing classical precision, which involves improving the accuracy of measurements or estimations within the realm of classical physics
BRCA2 Deficiency and Replication Stress Drive APOBEC3-Mediated Genomic Instability
No full textBRCA2 is a breast and ovarian cancer susceptibility gene that plays a major role in DNA damage repair in part by protecting the integrity of stalled replication forks. Mutations in BRCA2 are among the most common hereditary drivers of breast and ovarian cancer and significantly increases the lifetime cancer risk. Previous work from our group has shown that loss of BRCA2 impairs repair of stalled replication forks and leads to accumulation of single-stranded DNA (ssDNA) at stalled and collapsed replication forks. However, critical gaps remain in understanding how BRCA2 deficiency triggers fork collapse and how ssDNA accumulation in BRCA2-deficient cells leads to increased genomic instability remains unclear.
Using a novel uracil-in-DNA probe (U-DNA), we show that BRCA2 deficiency leads to an increased accumulation of uracil in ssDNA (U-ssDNA) at stalled forks. In keeping with high U-ssDNA accumulation, I observe an increase in abasic sites (AP-sites) upon replication stress in BRCA2-deficient cells. I identify APOBEC3 proteins (APOBEC3A and APOBEC3B) as key drivers of uracil accumulation in BRCA2-deficient cells through their cytosine deamination activity. Notably, replication stress induced by agents such as hydroxyurea or cisplatin, leads to upregulation of APOBEC3 proteins. Mechanistically, I show that ssDNA in BRCA2-deficient cells undergoing replication stress, serves as a trigger for the upregulation of A3A and A3B via the NF-kB pathway. Inhibition of the NF-kB signaling pathway using an inhibitor targeting both IKKα or IKKβ significantly downregulates A3A and A3B expression and decreases U-ssDNA levels. Interestingly, I find that unlike BRCA2-deficient cells, BRCA1-deficient cells do not accumulate AP-sites and do not upregulate A3A and/or A3B upon replication stress, highlighting the unique susceptibility of BRCA2-deficient cells to A3A/A3B upregulation.
I further demonstrate that sequential processing of AP sites in ssDNA by APE1 leads to stalled fork collapse, genomic instability and increased cell sensitivity to replication stress in BRCA2-deficient cells. Loss of A3A/3B or APE1 rescues genomic instability and cell viability in BRCA2-deficient cells undergoing replication stress. In keeping with this data, clinically, BRCA2-mutant ovarian tumors with low APE1 and/or high APOBEC and low APE1 levels correlate with worse prognosis. Overall, our findings establish upregulation of APOBEC3A/3B as a major driver of genomic instability in BRCA2 deficient tumors. Additionally, this work indicates that the levels of APOBEC3A/B and APE1 can influence BRCA2 mutant tumor evolution and response to therapy
The Role of Intolerance of Uncertainty in Prenatal Anxiety: Exploring Meta-cognitive and Psychosocial Moderators
Full text linkPrenatal anxiety is common and has been linked to myriad adverse psychological and physical health outcomes for both the pregnant individual and the child. While research on factors contributing to the etiology and maintenance of prenatal anxiety is limited, intolerance of uncertainty has been identified as a key factor related to anxiety during pregnancy. The current study aimed to substantiate the role of intolerance of uncertainty in prenatal anxiety and explore meta-cognitive and psychosocial constructs as potential moderators of the relation between intolerance of uncertainty and prenatal anxiety. Additionally, due to inconsistencies in the operationalization of prenatal anxiety in the current literature, these factors were examined in relation to both generalized anxiety symptoms and pregnancy-specific anxiety symptoms. A sample of 104 individuals (M age= 31.1, SD = 5.8; M gestational age= 21.8 weeks, SD = 9.8; 73% white) participated and completed online, self-report questionnaires assessing generalized and pregnancy-related anxiety symptoms, intolerance of uncertainty, mindfulness, experiential avoidance, and social support. Regression analyses revealed significant, positive relations between intolerance of uncertainty and both forms of prenatal anxiety. Similarly, mindfulness and experiential avoidance were significantly predictive of both forms of prenatal anxiety symptoms, while social support only significantly predicted generalized anxiety symptoms. None of the constructs tested were found to be significant moderators of the relation between intolerance of uncertainty and prenatal anxiety symptoms. It is important to note that current conclusions are limited due to collinearity between experiential avoidance and intolerance of uncertainty and the use of cross-sectional data. These findings underscore the need for further investigation into the clinical utility of meta-cognitive factors in the context of prenatal anxiety and provide further evidence that intolerance of uncertainty is a critical target for future prenatal anxiety intervention studies